Overexpression of EpCAM in uterine serous papillary carcinoma: implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201).
Overexpression of EpCAM in uterine serous papillary carcinoma: implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201).
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DOI：
10.1158/1535-7163.mct-09-0675
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发表时间：
2010-01
影响因子：
5.7
通讯作者：
Santin AD
中科院分区：
文献类型：
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作者：
El-Sahwi K;Bellone S;Cocco E;Casagrande F;Bellone M;Abu-Khalaf M;Buza N;Tavassoli FA;Hui P;Rüttinger D;Silasi DA;Azodi M;Schwartz PE;Rutherford TJ;Pecorelli S;Santin AD
我们评估了上皮细胞粘附分子（EpCAM）的表达和抗EpCAM的人单克隆抗体MT201 （adecatumumab）在子宫浆液性乳头状癌（USPC）中的潜力。采用real-time-PCR和免疫组化（IHC）技术检测56例USPC新鲜冷冻活检和石蜡包埋组织中EpCAM的表达。流式细胞术和免疫组化法检测了6株USPC细胞株中EpCAM的表面表达。在标准的5小时51Cr释放试验中，对表达不同水平EpCAM的一组原代USPC细胞系进行了MT201抗体依赖性细胞毒性（ADCC）和补体依赖性细胞毒性（CDC）的敏感性测试。与正常子宫内膜细胞（NEC）相比，EpCAM转录物在新鲜冷冻的USPC中显著过表达。肿瘤样本的中位（最小-最大）拷贝数为943.8(31.5-1568.3)，而NEC样本的中位（最小-最大）拷贝数为12.9 (1.0-37.0)（P < 0.001）。免疫组化结果显示，EpCAM在96%（26 / 27）的USPC样本中表达，与正常子宫内膜细胞相比，EpCAM的表达显著增加（P < 0.001）。流式细胞术检测的USPC细胞株中，有83%（6株中有5株）表面表达EpCAM。epcam阳性细胞系对mt201介导的ADCC高度敏感，而USPC原代细胞系对自然杀伤（NK）细胞依赖性细胞毒性具有抗性。人血浆IgG对mt201介导的USPC细胞毒性无明显抑制作用。EpCAM在子宫浆液癌中mRNA和蛋白水平均高表达，原发性USPC对mt201介导的细胞毒性高度敏感。MT201可能为晚期/复发或转移性USPC患者提供一种新的治疗策略。
We evaluated the expression of epithelial-cell-adhesion-molecule (EpCAM) and the potential of MT201 (adecatumumab), a human monoclonal antibody against EpCAM, in uterine serous papillary carcinoma (USPC). EpCAM expression was evaluated by real-time-PCR and immunohistochemistry (IHC) in a total of 56 USPC fresh-frozen biopsies and paraffin-embedded-tissues. EpCAM surface expression was also evaluated by flow cytometry and IHC in 6 USPC cell lines. Sensitivity to MT201 antibody-dependent-cellular-cytotoxicity (ADCC) and complement-dependent-cytotoxicity (CDC) was tested against a panel of primary USPC cell lines expressing different levels of EpCAM in standard 5-h 51Cr release-assays. EpCAM transcript was significantly overexpressed in fresh-frozen USPC when compared to normal-endometrial-cells (NEC). Median (minimum–maximum) copy number was 943.8 (31.5–1568.3) in tumor samples versus 12.9 (1.0–37.0) in NEC (P < 0.001). By immunohistochemistry, EpCAM expression was found in 96% (26 out of 27) of USPC samples with significantly higher expression compared to normal endometrial cells (P < 0.001). High surface expression of EpCAM was found in 83% (5 out of 6) of the USPC cell lines tested by flow cytometry. EpCAM-positive cell lines were found highly sensitive to MT201-mediated ADCC in vitro, while primary USPC cell lines were resistant to natural killer (NK) cell-dependent cytotoxicity. Human plasma IgG did not significantly inhibit MT201-mediated-cytotoxicity against USPC. EpCAM is highly expressed in uterine serous carcinoma at mRNA and protein levels and primary USPC are highly sensitivity to MT201-mediated cytotoxicity. MT201 might represent a novel therapeutic strategy in patients harboring advanced/recurrent or metastatic USPC refractory to standard treatment modalities.
影响因子：
8.8
作者：
Stein, R C;Malkovska, V;Morgan, S;Galazka, A;Aniszewski, C;Roy, S E;Shearer, R J;Marsden, R A;Bevan, D;Gordon-Smith, E C
通讯作者：
Gordon-Smith, E C